Vascular effects of ambient particulate matter instillation in spontaneous hypertensive rats
Vascular effects of ambient particulate matter instillation in spontaneous hypertensive rats
复制标题
DOI：
10.1016/j.taap.2004.02.005
复制
发表时间：
2004-05-15
影响因子：
3.8
通讯作者：
Borm, PJA
中科院分区：
文献类型：
--
作者：
Bagate, K;Meiring, JJ;Borm, PJA
暴露在环境颗粒物(PM)中与心血管损害人群的死亡率和发病率增加有关。本文研究了PM和脂多糖油对自发性高血压大鼠(SHR)灌胃后4h和24h血管功能的影响。用乙酰胆碱(ACh)和硝普钠(SNP)分别研究受体依赖性和非受体依赖性的松弛作用。我们已经使用苯肾上腺素(Phe)和KCI进行受体依赖和非依赖的收缩。用裸主动脉环研究内皮的作用。PM(EHC-93，10 mg/kg)或内毒素(350 EU/只/只)染毒后24~11天，大鼠肺部炎症反应最严重。与生理盐水组相比，PM和LPS可显著增加大鼠主动脉的受体依赖性血管舒张性。PM的作用在4小时后最大(EC50 ACh=2.3对5 NM对照组)，而在24小时影响较小(EC50 ACh=5.6对5 NM对照组)。SNP诱导的血管松弛作用仅在EHC-93处理的大鼠4h时增强(EC50=71.9比95.7 nM)，且高于24 h时的反应。但在有或无内皮的情况下，处理组之间在4h时无明显差异，而在内毒素滴注后的24h时，各处理组之间的差异无统计学意义。收缩曲线右移(EC50=65.3比43.3 nm)。KCI诱导的非受体依赖性血管收缩作用除24 h时内毒素组外，无明显变化，PM和模型颗粒包裹金属后，血管环也可直接松弛。血液金属分析显示，锌和钒浓度在滴注后1h和4h升高。结果表明，PM和内毒素对大鼠主动脉的舒缩作用是一过性的，在4h达到最大，而肺部炎症在24h达到最大，与血管松弛的损害相一致。目前的数据不允许在潜在机制之间进行区分，但表明金属的直接影响和炎症都起到了作用。(C)2004 Elsevier Inc.保留所有权利。
Exposure to ambient particulate matter (PM) is associated with increased mortality and morbidity among those people with cardiovascular impairment. We have Studied the effects of exposure to PM or lypopolysaccharide (LPS) oil ex vivo vascular function of spontaneous hypertensive rats (SHR) at 4 and 24 It post-instillation. Receptor-dependent and -independent relaxation was studied by using acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. We have used phenylephrine (Phe) and KCI for receptor-dependent and -independent contraction. The role of the endothelium was investigated using denuded aorta rings. Exposure to PM (EHC-93, 10 mg/kg) or LPS (350 EU/ animal) caused maximal pulmonary inflammation at 24 11 post-instillation. PM and LPS elicited a significant increase in receptor-dependent vasorelaxation of aorta compared to saline-instilled rats. The largest effect was seen with PM at 4 h post-instillation (EC50 ACh = 2.3 vs. 5 nM control), while at 24 h effects were Much smaller (EC50 ACh = 5.6 vs. 5 nM control). SNP-induced vasorelaxation was increased only in EHC-93-treated rats (EC50 = 71.9 vs. 95.7 nM) at 4 h, and this response was higher than that observed at 24 h. Phe induced a dose-dependent vasoconstriction. but no difference was seen between treatments in the presence or absence of endothelium at 4 h. However, at 24 h after instillation of LPS. a right shift of contraction Curve was seen (EC50 = 65.3 vs. 43.3 nM). No change was seen in receptor-independent vasoconstriction induced by KCI, except in the LPS group at 24 h. A direct relaxation was also observed upon in vitro exposure of aorta rings to PM, and model particles coated with metals. Blood metal analysis showed an increase of zinc and vanadium concentration at 1 and 4 h post-instillation. In conclusion, our data show that PM and LPS instillation has a transient effect on the vasorelaxation of rat aorta that is maximal at 4 h. On the other hand, Pulmonary inflammation reaches a maximum at 24 It and coincides with impairment of vasorelaxation. Current data do not allow discriminating among the potential mechanisms, but Suggest that both a direct effect of metals and inflammation play a role. (C) 2004 Elsevier Inc. All rights reserved.